Leukocyte-separating filter and leukocytes remover

ABSTRACT

A leukocyte remover includes a housing having a blood inlet, a blood outlet, and a leukocyte-separating filter disposed in the housing such that it partitions the interior of the housing into a blood inlet portion and a blood outlet portion. The leukocyte filter is composed of one or more three-dimensionally reticular, porous members with continuous open pores having a most frequent pore diameter of 1 μm to 5 μm and a ratio of a weight-average pore diameter to a number-average pore diameter in the range of 1.5 to 2.5.

BACKGROUND OF THE INVENTION

1. Field of the Present Invention

This invention relates to filters for separating leukocytes, leukocyteremovers, filters for separating both leukocytes and platelets, andleukocyte/platelet removers, and more particularly to those havingexcellent capability of capturing leukocytes without suffering fromcontamination with foreign matters.

2. Prior Art

In recent years, the form of blood transfusion has been changed fromconventional whole blood transfusion to blood component transfusion bywhich only a necessary component is transfused to a patient. Theimportant point of the blood component transfusion is how to increasethe purity of respective blood components fractionated.

Blood from donors has conventionally been centrifugally separated intoconcentrated red cells (CRC), a platelet concentrate (PC), and aplatelet-poor plasma (PPP). Blood preparations obtained by theseparation of blood are used for blood component transfusion to patientswho need red cells or platelets. However, since a large amount ofleukocytes are contained in blood preparations, problems may sometimestake place by injecting a large amount of leukocytes into patients bytransfusion.

Leukocytes contained in blood preparations must be removed to thepossible extent for the purpose of avoiding side effects, namelypost-transfusion reactions. To date, a number of improvements have beenproposed for this purpose. In some cases, extraction of red cells aloneby excluding leukocytes and platelets is also required. Used for thesepurposes are a method using a capturing member, a gravitationalcentrifugal separation method utilizing the difference in specificgravity between blood cells, a method utilizing the viscidity oradhesion of leukocytes, etc.

Among them, the method using a capturing member is widely used becauseof good efficiency in removing leukocytes or leukocytes and platelets,easiness of handling, etc. Capture members often used are fibers havingextremely small diameters such as natural fibers, synthetic fibers, etc.packed into a column, or non-woven fabrics formed bysecondary-processing them.

The use of such fibers, however, is likely to suffer from detachment ofsome fibers or outflow of foreign matters during operation. If the fiberpacking density is increased for the purpose of sufficiently capturingleukocytes or platelets, trapped blood cells tend to clog pores betweenthe fibers.

On the other hand, there are various proposals to use porous members asthe capturing members. For example, Japanese Patent Publication No.61-39060 discloses the use of a porous member including continuous finepores with an average pore diameter of 25 μm to 60 μm to capture highlyviscous monocytes and granulocytes. Japanese Patent Publication No.63-26089 discloses a method using a porous member having continuouspores with an average pore diameter of 5 μm to 20 μm to captureleukocytes by utilizing the viscidity of white cells and by filtrationwith the fine pores of the porous members.

However, in view of the recent demand for more effective removal ofleukocytes, the above porous members having relatively large porediameters do not provide satisfactory leukocyte separation.Leukocyte-separating abilities are elevated by reducing the porediameter (for example, by reducing the average pore diameter to lessthan 3 μm or so); however, blood cells trapped are likely to clog thepores of the porous members, taking much time for filtration.

Thus, there have so far been no leukocyte filters,leukocyte/platelet-separating filters, and removers comprising suchfilters with sufficient performance for the practical purpose, and theirimprovements are still desired.

OBJECTS AND SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide aleukocyte-separating filter suffering from no outflow of foreign mattersduring operation, having a high and stable capability of capturingleukocytes, and capable of efficiently and quickly separating leukocytesfrom blood or blood preparations.

Another object of the present invention is to provide aleukocyte/platelet-separating filter suffering from no outflow offoreign matters during operation, having a high and stable capability ofcapturing leukocytes and platelets, and capable of efficiently andquickly separating leukocytes and platelets from blood or bloodpreparations.

A still another object of the present invention is to provide aleukocyte remover comprising such a leukocyte-separating filter.

A still another object of the present invention is to provide aleukocyte/platelet remover comprising such aleukocyte/platelet-separating filter.

The first leukocyte-separating filter according to the present inventioncomprises as a major element a three-dimensionally reticular, porousmember having a three-dimensionally reticular, continuous texture withcontinuous open pores having a most frequent pore diameter in the rangeof 1 μm to 5 μm, and such a dust permeability that permits 200 or lessdust particles not smaller than 0.3 μm in the atmosphere to pass throughthe porous member in a period of time in which 100,000 of the same dustparticles flow without a filter (blank value).

The second leukocyte-separating filter according to the presentinvention comprises a three-dimensionally reticular, porous member withcontinuous open pores having a most frequent pore diameter in the rangeof 1 μm to 5 μm and a ratio of a weight-average pore diameter to anumber-average pore diameter in the range of 1.5 to 2.5.

The first leukocyte/platelet-separating filter according to the presentinvention comprises a platelet-adsorbing, three-dimensionally reticular,porous member with continuous open pores having a most frequent porediameter in the range of 1 μm to 5 μm and a ratio of a weight-averagepore diameter to a number-average pore diameter in the range of 1.5 to2.5.

The second leukocyte/platelet-separating filter according to the presentinvention comprises a laminate of at least one platelet-nonadsorbing,three-dimensionally reticular, porous member with continuous open poreshaving a most frequent pore diameter in the range of 1 μm to 5 μm and aratio of a weight-average pore diameter to a number-average porediameter in the range of 1.5 to 2.5, and at least oneplatelet-adsorbing, three-dimensionally reticular, porous member withcontinuous open pores having a most frequent pore diameter in the rangeof 1 μm to 5 μm and a ratio of a weight-average pore diameter to anumber-average pore diameter in the range of 1.5 to 2.5.

The leukocyte remover according to the present invention comprises ahousing having a blood inlet and a blood outlet; and aleukocyte-separating filter disposed in the housing such that itpartitions the interior of the housing into a blood inlet portion and ablood outlet portion, the leukocyte-separating filter being composed ofa three-dimensionally reticular, porous member with continuous openpores having a most frequent pore diameter in the range of 1 μm to 5 μmand a ratio of a weight-average pore diameter to a number-average porediameter in the range of 1.5 to 2.5.

The leukocyte/platelet remover according to the present inventioncomprises a housing having a blood inlet and a blood outlet; and aleukocyte/platelet-separating filter disposed in the housing such thatit partitions the interior of the housing into a blood inlet portion anda blood outlet portion, the leukocyte/platelet-separating filter being alaminate of at least one platelet-nonadsorbing, three-dimensionallyreticular, porous member with continuous open pores having a mostfrequent pore diameter in the range of 1 μm to 5 μm and a ratio of aweight-average pore diameter to a number-average pore diameter in therange of 1.5 to 2.5, and at least one platelet-adsorbing,three-dimensionally reticular, porous member with continuous open poreshaving a most frequent pore diameter in the range of 1 μm to 5 μm and aratio of a weight-average pore diameter to a number pore diameter in therange of 1.5 to 2.5.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is front elevational view showing a leukocyte remover including aleukocyte-separating filter according to an embodiment of the presentinvention;

FIG. 2 is a right side elevational view of FIG. 1;

FIG. 3 is a cross-sectional view taken along the A--A line in FIG. 1;

FIG. 4 is a front elevational view showing a leukocyte/platelet removerincluding a leukocyte/platelet-separating filter according to anembodiment of the present invention;

FIG. 5 is a right side elevational view of FIG. 4;

FIG. 6 is a cross-sectional view taken along the B--B line in FIG. 4;

FIG. 7 is a schematic view showing a circuit including theleukocyte-separating filter according to the present invention;

FIG. 8 is a schematic view showing another circuit including theleukocyte-separating filter according to the present invention;

FIG. 9 is a schematic view showing a circuit including theleukocyte/platelet-separating filter according to the present invention;

FIG. 10 is a schematic view showing another circuit including theleukocyte/platelet-separating filter according to the present invention;

FIG. 11 is a cross-sectional view showing a leukocyte-separating filterused in Examples and Comparative Examples;

FIG. 12 is a schematic view showing an experimental circuit with aleukocyte-separating filter used in Examples and Comparative Examples;

FIG. 13 is a graph showing the relation between a dust permeability anda leukocyte removal rate in leukocyte-separating filters; and

FIG. 14 is a schematic view showing an experimental circuit with aleukocyte-separating filter used in Examples and Comparative Examples.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

The present invention will be described below in detail.

[1] Leukocyte-separating filter

A leukocyte-separating filter explained in this Section is one forseparating leukocytes alone. A filter for separating both leukocytes andplatelets will be explained in Section [2].

The leukocyte-separating filter is composed of a three-dimensionallyreticular, porous member having continuous open pores whose mostfrequent pore diameter is 1 μm to 5 μm. If the most frequent porediameter is smaller than 1 μm, other blood cells contained in blood or aleukocyte suspension to be treated are also captured during leukocyteremoval operation, possibly clogging the filter. On the other hand, ifthe most frequent pore diameter is larger than 5 μm, the frequency ofcontact with a leukocyte suspension to be treated is lowered, possiblydecreasing the blood cell capturing rate. The more preferable mostfrequent pore diameter of the leukocyte-separating filter is 2 μm to 4μm.

The term "most frequent pore diameter" used herein means a pore diameterwhich the largest number of pores have, and it is defined as a mostfrequently occurring diameter (peak value) in a distribution of porediameters. The pore diameter distribution is obtained by cutting aporous member along an arbitrary surface, measuring cross section areasof respective pores distributed throughout the entirety of the crosssection surface, calculating diameters of the pores assuming that theyare converted into circular pores, and plotting the pore diameters on agraph in which the abscissa indicates pore diameters at 1-μm-intervalsand the ordinate indicates the number of pores in every interval (every1 μm). Thus, the most frequent pore diameter indicates a pore diametermost often shown, regarding all of the pores having variable shapes anddiameters as circular cross-sectional pores. In order to ensure areliability, not less than 2000 pores are preferably measured at random.

By the foregoing definition, the most frequent pore diameter does notnecessarily represent the largest diameter among those of the existingpores, but merely means that the number of pores having larger orsmaller diameters than the most frequent pore diameter graduallydecreases. Therefore, the most frequent pore diameter does not even meanthat particles having larger diameters do not pass through the porousmember. Although red cells in general have larger diameters than themost frequent pore diameter, living red cells can freely deform and passthrough the pores.

The three-dimensionally reticular, porous member with continuous openpores according to the present invention is characterized by having sucha dust permeability that permits 200 or less dust particles not smallerthan 0.3 μm in the atmosphere to pass through the porous member in aperiod of time in which 100,000 of the same dust particles flow withouta filter (blank value). If the dust permeability exceeds 200, theleukocyte removal rate decreases, and an expected leukocyte removal ratecannot be achieved. A preferable dust permeability is 20 or less.

The dust permeability is measured by the following method. First, aparticle counter ("KC-01" produced by RION) is set to operate under theconditions of one-liter evacuation, a flow rate of 500 cc/minute and ameasurable minimum particle size of 0.3 μm. After energized, theparticle counter is warmed up for at least 30 minutes. With the startbutton of the particle counter turned on, the period of time requiredfor counting 100,000 dust particles in the air is measured three times,and its average is taken as a blank value.

On the other hand, a porous member cut to a disc having a diameter of 47mm is set in a filter holder ("SWINEX 47" produced by MILLIPORE). Anupper portion of the filter holder equipped with the filter (porousmember) is connected to a tip end of a given vinyl chloride resin tubeattached to the particle counter. Then, with the start button of theparticle counter turned on, the number of dust particles passing throughthe filter in a period of time equivalent to the blank value ismeasured. The measurement is repeated three times for every filter, andthe average value is taken as the dust permeability.

By replacing the filter holder by a new one, next measurement is done.When the measurement of three filters are completed, the measurement ofa blank value is again done. If a new blank value is deviated from theprevious one, then measurement is continued with the new blank value.

In another embodiment, the porous member constituting theleukocyte-separating filter is characterized by having an average porediameter ratio (ratio of a weight-average pore diameter to anumber-average pore diameter) of 1.5 to 2.5. If the average porediameter ratio is less than 1.5, clogging is liable to occur, andfiltration takes much time. If it exceeds 2.5, the capturing rate isliable to decrease.

The weight-average pore diameter is a value defined by ΣRi² Ni/ΣRiNisimilarly to the equation of the weight average molecular weight, andthe number-average pore diameter is a value defined by ΣRiNi/ΣNi, whereRi is a pore diameter measured by a mercury infiltration method, and Niis the number of pores having a diameter Ri. The pore diameter Ri isdetermined by randomly cutting a porous member, measuring cross sectionareas of respective pores distributed throughout the entirety of thecross section surface, converting the cross sections of the pores tocircles, and calculating diameters of the circles. As explained above,the average pore diameter ratio represents a distribution of porediameters. The larger the value of the average pore diameter ratio, thewider the distribution of pore diameters, meaning that there are manypores having larger diameters than the most frequent pore diameter andmany pores having smaller diameters than the most frequent porediameter.

The porosity of a platelet-nonadsorbing, three-dimensionally reticular,porous member with continuous open pores is preferably 75% to 95% andmore preferably 80% to 95%, although it may vary depending on the mostfrequent pore diameter, etc. When the porosity is 75% or more,leukocytes are removed in a short time. If the porosity is 95% or less,a sufficient strength required for a filter is obtained. The thicknessof the porous member is preferably 0.1 mm to 10 mm and more preferablyabout 0.5 mm to about 3 mm, although it may vary depending on the mostfrequent pore diameter, porosity and microstructure of the porousmember. If the porous member is 0.1 mm or thicker, the filter is strongenough. On the other hand, if it is 10 mm or thinner, the length offiltration path is not excessive, and clogging is unlikely to occur.

The leukocyte-separating filter may be composed either of a singleporous member in the form of a flat sheet or of a plurality of suchporous members. Preferably, however, a plurality of flat porous membersare stacked to provide a laminate. In case where theleukocyte-separating filter is composed of a plurality of porousmembers, it is preferred to dispose one or more porous members havingwider pore diameter distributions (larger average pore diameter ratios)on the upstream side and one or more porous members having narrower porediameter distributions (smaller average pore diameter ratios) on thedownstream side. Placing the porous member having a wider pore diameterdistribution on the upstream side provides efficient separation ofleukocytes without increasing filtration resistance.

The three-dimensionally reticular, porous member with continuous openpores constituting the leukocyte-separating filter having the abovecharacteristics is made of a platelet-nonadsorbing material. The term"platelet-nonadsorbing" used herein means a characteristic of adsorbingsubstantially no platelet, and does not necessarily mean absolutenon-adsorption of platelets. Preferable materials therefor areethylene-vinyl alcohol copolymers, polyurethanes of any types includinga polyether type, a polyester type and a polycarbonate type (preferablypolyurethanes containing polyethers such as polytetramethylene oxide,polypropylene oxide or polyethylene oxide), fluorocarbon polymers(preferably polyvinylidene fluoride), polysulfones, and polyethersulfones. Particularly preferable are polyurethanes.

A preferable method for manufacturing the porous member is a so-calledelution method which comprises extruding a fiat sheet made of a resincomposition including a polymer such as polyurethane, polyvinylidenefluoride, polysulfone, polyester, polyamide, etc., a good solventtherefor and a pore-creating agent soluble in or swellable with anon-solvent having a compatibility with the good solvent, and thenimmersing the extruded flat sheet in the non-solvent to cause gelationwhile eluting out the pore-creating agent, thereby forming a fiat poroussheet or film having "through-pores", pores penetrating from one side tothe other of the porous sheet or film. A preferable ratio of the polymerin the resin composition is 5 weight % to 70 weight %. Preferable goodsolvents are dimethyl formamide, dimethyl sulfoxide, acetone, dioxane,methyl Cellosolve acetate, tetrahydrofuran, ethyl alcohol, methylalcohol, methyl ethyl ketone, etc. Preferable pore-creating agents arepolyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, polyether,polysaccharide, polyacrylic acid, etc. A preferable amount of thepore-creating agent added is 5 weight % to 50 weight % based on thecomposition to provide the porous member with continuous open pores(fine through-pores). This manufacturing method is described in detailin Patent Laid-open No. 3-47131. In the case of polyurethane, it may becoated on another material.

Since the leukocyte-separating filter of the present invention exhibitsa high and stable capability of capturing leukocytes, it can efficientlyand quickly separate leukocytes from a platelet concentrate (PC),concentrated red cells (CRC) or a whole blood without danger of outflowof foreign matters during operation. Further, the leukocyte-separatingfilter suffers from little variance in performance.

[2] Filter for Separating Leukocytes and Platelets

A filter for separating leukocytes and platelets(leukocyte/platelet-separating filter) may be either composed of one ormore platelet-adsorbing, three-dimensionally reticular, porous memberwith continuous open pores, or of a laminate of one or moreplatelet-nonadsorbing, three-dimensionally reticular, porous memberswith continuous open pores and one or more platelet-adsorbing,three-dimensionally reticular, porous members with continuous openpores. In any case, the porous members have a most frequent porediameter of 1 μm to 5 μm and an average pore diameter ratio (ratio of aweight-average pore diameter to a number-average pore diameter) of 1.5to 2.5 in order to have a good leukocyte-separating capability. For thesame reason as stated above, the most frequent pore diameter ispreferably 2 μm to 4 μm.

The platelet-nonadsorbing, three-dimensionally reticular, porous memberwith continuous open pores may be the same as explained in [1] above. Incontrast, the platelet-adsorbing, three-dimensionally reticular, porousmember with continuous open pores may be made either of aplatelet-adsorbing material or of a cationic-treatedplatelet-nonadsorbing or platelet-adsorbing material.

Platelet-adsorbing materials usable in the present invention arepolyvinyl acetals (preferably polyvinyl formal), aliphatic polyamideswhich may be nylon 6, nylon 66, nylon 12, or so-called polyetheramidescopolymerized with polyether components such as polytetramethyleneoxide, polypropylene oxide and polyethylene oxide, aromatic polyamides(preferably, in particular, polymethaphenylene isophthalic amide orpolyparaphenylene terephthalic amide), polyesters (in particularpolybutylene terephthalate, polyethylene terephthalate, etc.),polyimides, etc.

The term "cationic treatment" used herein means to adhere or bond acationic compound to a surface of a filter substrate or to incorporatethe cationic compound into the filter substrate. Specifically, there aremethods of coating the porous member with a cationic compound, methodsof bonding the cationic compound to the filter substrate by graftingcopolymerization, etc., and methods of mixing the filter substrate withthe cationic compound in the process of fabrication of the porousmember. Cationic compounds usable are quaternary ammonium salts,compounds having amino groups or imino groups, etc. For example, in apreferable method for bonding the cationic compound to the filtersubstrate by graft copolymerization, the filter substrate is subjectedto a plasma treatment, and graft-copolymerized with a monomer having areactive substituent such as glycidyl methacrylate, and then a cationicagent is bonded to the grafted monomer. Cationic treatment contributesto maintaining a positive charge of the filter for a long period oftime.

The porous member constituting the leukocyte/platelet-separating filter,either platelet-nonadsorbing or platelet-adsorbing, preferably has apermeability of 200 or less for dust particles of 0.3 μm or larger as inthe case of [1] above.

The platelet-adsorbing three-dimensionally reticular, porous member withcontinuous open pores has a porosity of 75% to 95% and a thickness of0.1 mm to 10 mm for the reason described in [1] above.

The platelet-adsorbing, three-dimensionally reticular, porous memberwith continuous open pores may be produced by any method, provided thatthe porous member has the aforementioned structure. A preferable methodis an elution method. In the case of making the porous member ofpolyvinyl formal, for example, the elution method uses an acetal-formingreaction by which formaldehyde and an acid catalyst acts on an aqueouspolyvinyl alcohol solution containing a pore-creating agent selectedfrom amylose-containing polysaccharide such as starch and dextrin,derivatives thereof, acid-proof anionic surfactants, nonionicsurfactants, etc. optionally in the presence of an inorganic salt suchas sodium sulfate, sodium chloride, ammonium sulfate, ammonium chloride,potassium sulfate, sodium iodide, etc. (Patent Publication Nos. 47-46455and 48-20019).

With a high and stable capability of capturing leukocytes and platelets,the leukocyte/platelet-separating filter of the present invention canefficiently and quickly separate leukocytes and platelets fromconcentrated red cells (CRC) and a whole blood, without danger ofoutflow of foreign matters during operation. It also reduces variance inperformance.

[3] Leukocyte Remover

A leukocyte remover equipped with the leukocyte-separating filteraccording to the present invention will be explained below in detailwith reference to FIGS. 1 to 3. FIG. 1 is a front elevational view of anexample of the leukocyte remover with the leukocyte-separating filteraccording to the present invention, FIG. 2 is a right side elevationalview of FIG. 1, and FIG. 3 is a cross-sectional view taken along theA--A line in FIG. 1.

The leukocyte remover 1 with the leukocyte-separating filter 6 accordingto the present invention is composed of a housing 2 having blood inlet2a and a blood outlet 2b, and a leukocyte-separating filter 6constituted by a three-dimensionally reticular, porous member withcontinuous open pores and disposed in the housing 2 such that itpartitions the interior of the housing 2 into a blood inlet portion 3aand a blood outlet portion 3b. As shown in FIG. 3, the filter 6 of thepresent invention is received in the housing 2 such that blood, etc.introduced into the housing 2 through the blood inlet 2a cannot exitfrom the blood outlet 2b without passing through the filter 6. Acircumferential portion of the filter 6 is water-tightly disposedbetween inner surfaces of two members of the housing 2. The filter 6, asshown in FIG. 3, is partly clumped by a plurality of projections 2cformed on the inner surface of the two constituent members of thehousing 2 to prevent deformation of the filter during operation andstorage.

Usable for the housing 2 are various materials such as polycarbonates,acrylic resins, polyethylene terephthalate, polyethylene, polypropylene,polystyrene, polyvinyl chloride resins, acryl-styrene copolymers,acryl-butylene-styrene copolymers, and so on. Particularly preferableare polycarbonates, acrylic resins, polyethylene terephthalate,polyethylene, polypropylene, polystyrene and polyvinyl chloride resins.The inner surface of the housing 2 is preferably treated to have ahydrophilic nature to alleviate adhesion of blood cells thereto.Suitable hydrophilic treatment is coating or bonding of a hydrophilicsubstance, or a surface treatment such as plasma treatment, coronatreatment, etc.

In the leukocyte remover 1 according to one embodiment of the presentinvention shown in FIG. 3, a pre-filter portion (the right side portionof the filter 6 in FIG. 3) on the upstream side of a main filter portion(the left side portion of the filter 6 in FIG. 3) functions to removefine particles in the blood (for example, gels, microaggregates, etc.)and huge leukocyte particles among all leukocytes from the blood, beforeintroducing the blood into the main filter portion to prevent cloggingof the main filter portion.

A suitable porous member used for the pre-filter portion is athree-dimensionally reticular, porous member with continuous open poreshaving a most frequent pore diameter of about 2 μm to about 4 μm, anaverage pore diameter ratio of 2.0 to 2.5, and a thickness of about 0.3mm to about 1.5 mm. A suitable number of such porous members laminatedis 1 to 5. A suitable porous member used for the main filter portion isa three-dimensionally reticular, porous member with continuous openpores having a most frequent pore diameter of about 1 μm to about 3 μmand smaller than that of the pre-filter portion, an average porediameter ratio of 1.5 to 2.0, and a thickness of about 0.3 mm to about1.5 min. A suitable number of such porous members laminated is 1 to 5.

In a preferred embodiment, the pre-filter portion may be made bystacking two porous polyurethane films each having a most frequent porediameter of 2.5 μm to 3.5 μm, an average pore diameter ratio of 2.5, anda thickness of about 0.6 mm and treated by a surfactant, and the mainfilter portion may be made by stacking four porous polyurethane memberseach having a most frequent pore diameter of 1.0 μm to 2.0 μm, anaverage pore diameter ratio of 1.7, and a thickness of about 0.6 mm andtreated by a surfactant.

The filter may be a single-layered member in lieu of the laminate statedabove. The thinner the filter, the easier it is to make the integralstructure uniform, and the easier the fabrication of a filter meetingthe desired numerical conditions. Further, taking intended use, sheetareas and other factors into consideration, any appropriate number ofsheets may be laminated to make a desired leukocyte remover. The numberof porous sheets laminated may appropriately be determined byconsidering the removal rate, filtration time, likelihood of clogging,etc.

Any surfactant may be used for a hydrophilic treatment, and suitablyusable are, for example, glycerol monolaurate, and polyether-typesurfactants (for example, Pluronic surfactant). Instead of using asurfactant, the porous member may be hydrophilic-treated (for example,plasma-treated).

An example of usage of the leukocyte-separating filter 6 of the presentinvention will be explained below with reference to FIG. 7 showing acircuit for removing leukocytes from a blood preparation such asplatelet concentrate which does not contain red cells for componenttransfusion of platelets to a patient.

The separation of leukocytes with the circuit of FIG. 7 is started byclosing clamps 20a, 20b. Protectors 21a, 21b are then removed, andneedles 22a, 22b are attached to a bag (not shown) of a bloodpreparation (specifically, platelet concentrate) and to a rinse bag (notshown). The blood preparation bag and the rinse bag are hung down froman irrigator (not shown).

While maintaining the leukocyte remover 1 upside down, the clamps 20aand a roller clamp 23 are opened for priming the leukocyte remover 1.After the priming of the leukocyte remover 1 is completed, the leukocyteremover 1 is returned to the original posture. After that, by making aninstillator 24 upside down, the blood preparation is introduced into theinstillator 24. After the blood preparation occupies about a half volumeof the instillator 24, the instillator 24 is returned to the originalposture. When the blood preparation reaches a tip end of a lockconnector 25, the roller clamp 23 is closed.

With a syringe needle attached to the end of the lock connector 25,instillation (component transfusion, i.e. platelet transfusion in thiscase) into the vein of a patient is started. The flow rate ofinstillation is adjusted by the roller clamp 23.

When the blood preparation bag is emptied, the roller clamp 23 is closedand the clamp 20b is opened to introduce a rinse into the bloodpreparation bag. When 100 ml or so of the rinse is introduced, the clamp20b is closed and the roller clamp 23 is again opened to resume thecomponent transfusion. When the rinse in the blood preparation bag isexhausted, the rinse in the inlet-side tube 27 is recovered by openingan air vent 26, and the transfusion is finished.

Another example of usage of the leukocyte-separating filter 6 of thepresent invention will be explained below with reference to FIG. 8. Thecircuit of FIG. 8 uses the leukocyte-separating filter 6 of the presentinvention to remove leukocytes and recover platelets from a bloodpreparation not including red cells, such as a platelet concentrate. Theseparation of leukocytes by the circuit is substantially the same asthat explained above, except for differences in that transfusion usingthe rinse is conducted and that the remover 1 does not include the airvent 12d whose function in the process stated above is performed by anair vent 37a. Incidentally, transfusion using a rinse may not beconducted in the circuit comprising leukocyte remover 1, and theleukocyte remover 1 may have the air vent 12d.

[4] Leukocyte/platelet remover

A leukocyte/platelet-separating filter and a leukocyte/platelet removercomprising the leukocyte/platelet-separating filter according to thepresent invention will be explained below with reference to thedrawings. FIG. 4 is a front elevation showing an example of theleukocyte/platelet remover comprising the leukocyte/platelet-separatingfilter according to the present invention. FIG. 5 is a right sideelevational view of FIG. 4. FIG. 6 is a cross-sectional view taken alongthe B--B line in FIG. 4.

The leukocyte/platelet remover 10 comprising theleukocyte/platelet-separating filter 16 of the present inventionincludes a housing 12 having a blood inlet 12a and a blood outlet 12b,and the leukocyte/platelet-separating filter 16 disposed in the housing2 such that it partitions the interior of the housing 12 into a bloodinlet portion 13a and a blood outlet portion 13b. Theleukocyte/platelet-separating filter 16 is composed of a pre-filter 16afor removing microaggregates and gels occurring in stored blood, and aplatelet-adsorbing, three-dimensionally reticular, porous member withcontinuous open pores (main filter) 16b having a most frequent porediameter of 1 μm to 5 μm and a ratio of a weight-average pore diameterto a number-average pore diameter in the range of 1.5 to 2.5. With thisstructure, the main filter 16 exhibits a good ability to capture bothleukocytes and platelets.

The pre-filter 16a is preferably composed of non-woven fabrics in theform of a flat sheet each having a weight/area value of 30 g/m² to 80g/m², an average fiber diameter of 10 μm to 20 μm and a thickness ofabout 0.3 mm to about 0.6 mm. Two to five such non-woven fabrics arepreferably laminated. The main filter portion is preferably composed ofa primary main filter portion having a wider pore diameter distributionand a secondary main filter portion having a narrower pore diameterdistribution. The primary main filter portion is preferably composed ofthree-dimensionally reticular, porous members with continuous open poreseach having a most frequent pore diameter of about 2 μm to about 3 μm,an average pore diameter ratio of 1.8 to 2.5 and a thickness of about0.5 mm to about 2 mm. Two to five such porous members are preferablylaminated. The secondary main filter portion is preferably composed ofthree-dimensionally reticular, porous members with continuous open poreseach having a most frequent pore diameter of about 2 μm to about 3 μm,an average pore diameter ratio of 1.5 to 2.1 and a thickness of about0.2 mm to about 2 mm. Two to five such porous members are preferablylaminated. The porous members used for the secondary main filter portionmay be the same as those used for the primary main filter portion.

In a preferred example, the pre-filter 16a is made by stacking threesheets of non-woven polyester fabrics each having an average fiberdiameter of 12 μm and a bulk density of 0.1875 g/cm³ or so to athickness of about 0.1 mm. An upstream portion of the main filter 16b(the right side portion of the main filter 16b in FIG. 6) constitutes aprimary main filter portion made by stacking on a 0.2-mm-thick sheet ofnon-woven polyester fabrics as a support member threesurfactant-treated, porous polyurethane films each having a mostfrequent pore diameter of 1.0 μm to 3.0 μm, an average pore diameterratio of 2.0 and a thickness of about 1.0 mm. A downstream portion ofthe main filter 16b (the left side portion of the main filter 16b inFIG. 6) constitutes a secondary main filter portion made by stackingthree porous polyurethane films identical to those of the upstreamportion but subjected to a cationic treatment and a surfactanttreatment. Thus, the leukocyte/platelet-separating filter 16 of thepresent invention is preferably made by laminating a plurality of suchporous members. The number of porous sheets stacked may be appropriatelydetermined, considering such factors as removal rate, filtration timeand likelihood of clogging.

Any surfactants may be used for a hydrophilic treatment, and suitablesurfactants are, for example, deca-glycerol monolaurate, andpolyether-type surfactants (for example, Pluronic surfactant). Insteadof using a surfactant, the porous member may be subjected to ahydrophilic treatment (for example, plasma treatment).

The pre-filter 16a is used to remove microaggregates and gels originallycontained in the blood or generated in the blood due to aggregationduring storage. The porous member constituting the primary main filterportion disposed on the upstream side functions to remove leukocyteshaving larger diameters than its own pore diameters. Negative-chargedplatelets have smaller diameters than those of the porous memberconstituting the secondary main filter portion disposed on thedownstream side. Nevertheless, since the porous member of the secondarymain filter portion is positive-charged by a cationic treatment,platelets are electrically trapped by the porous member. Leukocytespassing through the primary main filter portion, although very few, arealso removed by the secondary main filter portion. Also, red cellshaving larger diameters than the pore diameters of the porous membersconstituting the primary and secondary main filter portions can passthrough the main filter 16b, because they are easily deformable.

Reasons why the porous member of the main filter 16b is combined withthe non-woven fabrics are, among others, that the nonwoven fabricshaving little anti-thrombogenic nature function to adsorb highlyadherent platelets, that a step for stripping them in the sheetfabricating process can be omitted, that the porous member can be moreeasily mounted in the housing 2, and that the non-woven fabrics keep theporous member in a proper shape.

As shown in FIG. 6, the housing 12 of the leukocyte/platelet remover 10has an air vent 12d near an upper portion. The air vent 12d facilitatesthe removal of an air in the course of priming the remover 10, theoperation of starting or stopping filtration, the recovery of residualliquids in the remover, the removal of an air from the recovery bag, andso forth. Although the air vent 12d used in this embodiment can beopened and closed by a cap, it may be configured otherwise.

An example of usage of the leukocyte/platelet-separating filter 16according to the present invention will be explained below withreference to FIG. 9. The leukocyte/platelet remover 10 with theleukocyte/platelet-separating filter 16 according to the presentinvention is connected in a circuit as shown, for example, in FIG. 9.The circuit shown in FIG. 9 is for use in component transfusion of redcells to a patient while removing leukocytes and platelets from a wholeblood or a blood preparation including red cells (for example,concentrated red cells) by using the leukocyte/platelet remover 10including the leukocyte/platelet-separating filter 16 according to thepresent invention.

The process of separation of leukocytes and platelets by this circuit isthe same as those stated above, except that transfusing operation by arinse is not performed, and that the air vent 12d of the remover 10 isopened to transfuse red cells remaining in the tube on the outlet sideto a patient after the blood preparation bag is emptied. The circuitcomprising the leukocyte/platelet remover 10 may also be used fortransfusing operation by a rinse, and the leukocyte/platelet remover 10may not necessarily have the air vent 12d.

Another example of usage of the leukocyte/platelet-separating filter 16of the present invention will be explained with reference to FIG. 10.The circuit shown in FIG. 10 is intended to remove leukocytes andplatelets and recover red cells from a whole blood or blood preparationsincluding red cells by using the leukocyte/platelet remover 10comprising the leukocyte/platelet-separating filter 16.

The process of separation of leukocytes by this circuit is conducted byopening a peel tab 30 and attaching a needle 33 of a recovery bag 32 toa vent 31, closing clamps 34a, 34b and a cap 14 of the air vent 12d,removing a protector 35, attaching a needle 36 to a blood preparationbag (not shown), and hanging it down from an irrigator (not shown).

The clamps 34a and the cap 14 of the air vent 12d are then opened forpriming the remover 10. When the blood preparation reaches the air vent12d, the air vent 12d is closed by the cap 14, and the clamp 34b isopened, thereby starting filtration.

When the blood preparation bag is emptied, a residual blood preparationon the inlet side is recovered by opening the air vent 37, and aresidual blood preparation on the outlet side is recovered by openingthe cap 14 of the air vent 12d. The residual blood preparation in thetube 38' on the outlet side is recovered in the bag 32 by squeezing thetube 38 with roller pincers. If there is a need for removal of an airfrom the recovery bag 32, the air can be expelled from the recovery bag32 through the air vent 12d by moving the air toward the tube 38 andthen pressing the recovery bag 32. Sealing the tube 38, the recovery bag32 is detached from the circuit to finish the process of separatingleukocytes and platelets.

The present invention will be explained in greater detail by way ofExamples below without intention of limiting the present inventionthereto.

EXAMPLE 1

A leukocyte-separating filter having the construction shown in FIG. 11was made by using a porous polyvinyl formal sheet having a most frequentpore diameter of 2 μm to 3 μm, a dust permeability of 5, a porosity of86%, a thickness of 1.3 mm and a filtration area of 50 cm², and thefilter was mounted to the circuit of FIG. 12. In FIGS. 11 and 12, 41denotes a leukocyte-separating filter, 42a a blood inlet, 42b a bloodoutlet, 43 a housing, 44 a porous polyvinyl formal member, 45a and 45bsupport members, 46 a blood bag, 46a a physiological saline solutionbag, 47 a blood recovery bag, 47a a physiological saline solutionrecovery bag, 48a, 48b, 48c and 48d clamps, and 49a, 49b, 49c and 49dliquid tubes.

A unit of CPD-added concentrated red cells (CRC) obtained from 400 ml ofthe human blood was caused to flow through the separating filtergravitationally. The time required for the treatment was 6 minutes. Thenumbers of blood cells in CRC before and after the treatment weremeasured with an automatic blood cell counter (Sysmex NE-6000 producedby Toa Medical Electronics Co., Ltd.). The total numbers of respectiveblood cell components were measured on a liquid volume basis, and thered cell recovery rate and the leukocyte removal rate were determined.As a result, the red cell recovery rate was 98%, and the leukocyteremoval rate was 90%.

EXAMPLE 2

A leukocyte-separating filter having the construction shown in FIG. 11was made by using a porous polyurethane film having a most frequent poresize of 2 μm to 3 μm, a dust permeability of substantially zero, aporosity of 82%, a thickness of 1.0 mm and a filtration area of 50 cm²,and the filter was mounted to the circuit of FIG. 12.

Ten units of CPD-added concentrated platelet concentrate (PC) obtainedfrom 200 ml of the human blood were caused to flow through theseparating filter gravitationally at an instillation speed of about 4ml/minute. As a result, the drop speed did not decrease. The numbers ofblood cells in PC before and after the treatment were measured with anautomatic blood cell counter (Sysmex NE-6000 produced by Toa MedicalElectronics Co., Ltd.) and a flow cytometer (Cyto-ACE 150 produced byNippon Bunko K. K.). The total numbers of respective blood cellcomponents were measured on a liquid volume basis, and the leukocyteremoval rate and the platelet recovery rate were determined. Theleukocyte removal rate was 99.9% and the platelet recovery rate was 95%.

EXAMPLE 3

Dust permeability was measured on porous polyvinyl formal members eachhaving a most frequent pore diameter of 2 μm to 3 μm, a thickness of 1.3mm and a porosity of 80% to 87% (A to F indicated by white circles inFIG. 13), and on porous polyvinyl formal members each having a mostfrequent pore diameter of 8 μm to 9 μm, a thickness of 1.3 mm and aporosity of 80% to 87% (G and H indicated by black circles in FIG. 13).

A leukocyte-separating filter having the construction shown in FIG. 11(having a filtration area of 100 cm²) was composed of the above porousmembers, and it was mounted to the circuit of FIG. 12. One unit ofCPD-added concentrated red cells (CRC) obtained from 400 ml of the humanblood was caused to flow through the separating filter gravitationally.The numbers of blood cells in CRC before and after the treatment weremeasured with an automatic blood cell counter (Sysmex NE-6000 producedby Toa Medical Electronics Co., Ltd.). The total numbers of respectiveblood cell components were measured on a liquid volume basis, and theleukocyte removal rate was determined. The results are shown in Table 1and FIG. 13.

                  TABLE 1                                                         ______________________________________                                        Filter                                                                        ______________________________________                                                         A      B        C    D                                       ______________________________________                                        Most Frequent Pore                                                                             2-3    2-3      2-3  2-3                                     Diameter                                                                      Dust Permeability                                                                               1      13       104  518                                    Leukocyte Removal Rate                                                                         99.7   99.3     98.9 94.5                                    ______________________________________                                                         E      F        G    H                                       ______________________________________                                        Most Frequent Pore                                                                             2-3    2-3      8-9  8-9                                     Diameter                                                                      Dust Permeability                                                                              617    782      2459 2821                                    Leukocyte Removal Rate                                                                         88.1   89.6     61.8 52.0                                    ______________________________________                                    

The above results proved that filters composed of porous members whosemost frequent pore diameters were in the range of 2 μm to 3 μm had smalldust permeabilities and good leukocyte removal rates, while filterscomposed of porous members whose most frequent pore diameters were inthe range of 8 μm to 9 μm provided large dust permeabilities and lowleukocyte removal rates. Incidentally, the red cell recovery rate was98% or more in all of the filters.

EXAMPLES 4-9, COMPARATIVE EXAMPLES 1-4

Leukocyte/platelet-separating filters having the construction shown inFIG. 4 were made by using porous polyvinyl formal members having athickness of 1.3 mm, a filtration area of 50 cm², and most frequent porediameters and average pore diameter ratios shown in Table 2. Since theporous polyvinyl formal members are hydrophilic and platelet-adsorbing,they were not subjected to any particular hydrophilic treatment andcationic treatment.

Every two of the porous members shown in Table 2 were stacked to make aleukocyte/platelet-separating filter, which was then assembled in aleukocyte/platelet remover as shown in FIG. 6. Each of suchleukocyte/platelet removers was mounted to the circuit having thestructure shown in FIG. 10. 0.5 units of CPD-added concentrated redcells (CRC) obtained from 400 ml of the human blood were caused to flowthrough the separating filter gravitationally.

The numbers of blood cells in CRC before and after the treatment, andthe numbers of red cells and platelets after the treatment were measuredwith an automatic blood cell counter (Sysmex NE-6000 produced by ToaMedical Electronics Co., Ltd.). The total numbers of respective bloodcell components were measured on a liquid volume basis, and the red cellrecovery rates and the platelet removal rates were determined.

The numbers of leukocytes after the treatment were measured with a flowcytometer (Cyto-ACE 150 produced by Nippon Bunko K. K.) and a Nageottehemocytometer. The total number of leukocytes was measured on a liquidvolume basis, and the removal rate of leukocytes was determined. Theresults are shown in Table 3.

                  TABLE 2                                                         ______________________________________                                                  Porous Member                                                                   Most Frequent Average Pore                                        No.         Pore Diameter (μm)                                                                       Diameter Ratio                                      ______________________________________                                        Example 4   1.0           2.0                                                 Example 5   2.0           1.9                                                 Example 6   3.5           1.8                                                 Example 7   4.0           1.7                                                 Example 8   4.5           2.5                                                 Example 9   5.0           2.0                                                 Com. Ex. 1  0.5           2.1                                                 Com. Ex. 2  2.0           1.4                                                 Com. Ex. 3  6.0           1.4                                                 Com. Ex. 4  6.0           2.0                                                 ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                               Separation Results                                                              Filtering                                                                              Leukocyte  Red Cell                                                                              Platelet                                          Time     Removal    Recovery                                                                              Removal                                  No.      (minute) Rate (%)   Rate (%)                                                                              Rate (%)                                 ______________________________________                                        Example 4                                                                              14       99.9       97      92                                       Example 5                                                                              12       99.9       97      92                                       Example 6                                                                              11       99.9       97      91                                       Example 7                                                                              10       99.9       97      91                                       Example 8                                                                               8       99.5       98      90                                       Example 9                                                                              10       99.7       98      90                                       Com. Ex. 1                                                                             53       99.9       94      93                                       Com. Ex. 2                                                                             47       99.9       92      92                                       Com. Ex. 3                                                                              6       93.2       99      82                                       Com. Ex. 4                                                                              5       91.0       99      77                                       ______________________________________                                    

Table 3 proves that the leukocyte/platelet-separating filters ofExamples 4 to 9 composed of porous members having most frequent porediameters in the range of 1 μm to 5 μm and average pore diameter ratiosin the range of 1.5 to 2.5 exhibit good leukocyte removal rates in apractical period of time, and that their red cell recovery rates andplatelet removal rates are better than those of Comparative Examples 1to 4.

The same experiment was conducted with porous polyurethane membershaving a porosity of about 87%, a thickness of 1.3 mm, a filtration areaof 50 cm², and most frequent pore diameters and average pore diameterratios shown in Table 2. As a result, substantially the same resultswere obtained. Incidentally, a primary filter portion of theleukocyte/platelet-separating filter was produced by stacking threeporous polyurethane members subjected to a hydrophilic treatment withglycerol monolaurate (decaglycerin monolaurate). A secondary filterportion of the leukocyte/platelet-separating filter was produced byusing the same porous members as in the primary filter portion, bysubjecting them to a plasma treatment, graft copolymerization withglycidyl methacrylate, fixing of a cationic agent (Cationon UK producedby Ipposha Oil & Fat Industries K. K.) and then a treatment withglycerol monolaurate, and by stacking three of them. The housing usedwas configured as shown in FIGS. 4 to 6. The housing contained theseparating filter to form the leukocyte/platelet remover as shown inFIG. 6.

EXAMPLES 10-13, COMPARATIVE EXAMPLES 5-7

A leukocyte/platelet-separating filter shown in FIG. 14 was made byusing porous polyurethane members having a thickness of 0.6 mm, afiltration area of 3 cm², a porosity of about 87%, and most frequentpore diameters and average pore diameter ratios shown in Table 4. Thefilter included a pre-filter portion made by stacking two such porousmembers shown in Table 4 subjected to a hydrophilic treatment withglycerol monolaurate, and a main filter portion made by stacking foursuch porous members treated by glycerol monolaurate like those of thepre-filter portion. The housing used was configured as shown in FIG. 14,and contained the above separating filter to form a leukocyte remover.

The leukocyte-separating filters of Examples 10 to 13 and ComparativeExamples 5 to 7 were incorporated into circuits having the constructionshown in FIG. 14 to form experimental circuits. Lymphocyte-containing,platelet-rich plasma (PRP) (platelets: 3.5×10⁵ /μl-5.5×10⁵ /μl, andleukocytes: 3.5×10³ /μl-4.5×10³ /μl) was prepared by addingself-lymphocytes separated by a density-gradient centrifugal separationmethod to a platelet-rich plasma (PRP) collected from CPD-added freshblood of healthy humans. The experiment was conducted by passing thelymphocyte-containing PRP through the experimental circuits shown inFIG. 14 at a flow rate of 1 ml/minute.cm².

The numbers of platelets in PRP before and after the treatment and thenumbers of leukocytes in PRP before the treatment were measured with anautomatic blood cell counter (Sysmex NE-6000 produced by Toa MedicalElectronics Co., Ltd.), and the number of leukocytes after the treatmentwas measured with a flow cytometer (Cyto-ACE 150 produced by NipponBunko K. K.) and a Nageotte hemocytometer. The total numbers ofrespective blood cell components were measured on a liquid volumesbasis, and the leukocyte removal rates and the platelet recovery rateswere calculated therefrom. The results are shown in Table 5.

                  TABLE 4                                                         ______________________________________                                               Porous Member                                                                 Pre-filter Portion                                                                              Main Filter Portion                                           Most     Average    Most   Average                                            Frequent Pore       Frequent                                                                             Pore                                               Pore     Diameter   Pore   Diameter                                  No.      Diameter Ratio      Diameter                                                                             Ratio                                     ______________________________________                                        Example 10                                                                             3.5 μm                                                                              1.8        1.0 μm                                                                            2.0                                       Example 11                                                                             3.5 μm                                                                              1.8        2.0 μm                                                                            1.9                                       Example 12                                                                             4.0 μm                                                                              1.7        2.0 μm                                                                            1.9                                       Example 13                                                                             4.5 μm                                                                              2.5        1.0 μm                                                                            2.0                                       Com. Ex. 5                                                                             5.0 μm                                                                              2.0        1.0 μm                                                                            2.0                                       Com. Ex. 6                                                                             6.0 μm                                                                              2.0        0.5 μm                                                                            2.1                                       Com. Ex. 7                                                                             6.0 μm                                                                              2.0        2.0 μm                                                                            1.4                                       ______________________________________                                    

                  TABLE 5                                                         ______________________________________                                                 Separation Results                                                              Leukocyte     Platelet                                             No.        Removal Rate (%)                                                                            Recovery Rate (%)                                    ______________________________________                                        Example 10 99.99         91                                                   Example 11 99.99         93                                                   Example 12 99.99         92                                                   Example 13 99.99         91                                                   Com. Ex. 5 99.75         91                                                   Com. Ex. 6 --*           --*                                                  Com. Ex. 7 99.23         94                                                   ______________________________________                                         Note: *No flow by clogging.                                              

Table 5 proves that the leukocyte filters of Examples 10 to 13 composedof porous members having most frequent pore diameters in the range of 1μm to 5 μm and average pore diameter ratios in the range of 1.5 to 2.5exhibited better leukocyte removal rates and platelet removal rates thanthose of Comparative Examples 5 to 7.

As explained above, since the leukocyte-separating filters of thepresent invention are composed of three-dimensionally reticular, porousmember with continuous open pores having most frequent pore diametersranging from 1 μm to 5 μm and a permeability of 200 or less for dustparticles having diameters not less than 0.3 μm in the air, they exhibithigh and stable abilities to capture leukocytes. Thus, leukocytescontained in the blood are efficiently and quickly captured when passingthrough complicated flow paths of continuous open pores in the matrix ofthe porous member. By meeting the requirement that the ratio of aweight-average pore diameter to a number-average pore diameter is in therange of 1.5 to 2.5, the leukocyte removal rate is further improved.Since the flow path of the filter is defined by the three-dimensionallyreticular, continuous texture of a porous member (continuous open poresdefined by the matrix of the porous member), the filter is stable anduniform in performance. The filter also suffers from substantially nooutflow of foreign matters from the porous members and channeling of theflow paths during operation. Moreover, since the flow paths of thefilter are formed at the time of production of the porous member, thefilter can very easily be fabricated.

What is claimed is:
 1. A leukocyte-separating filter composed of aplurality of three-dimensionally reticular, porous members withcontinuous open pores having a most frequent pore diameter in the rangeof 1 μm to 5 μm and a ratio of a weight-average pore diameter to anumber-average pore diameter in the range of 1.5 to 2.5, one or more ofsaid porous members located on the upstream side having a ratio of theweight-average pore diameter to the number-average pore diameter largerthan that of the remaining porous members located on the downstreamside.
 2. The leukocyte-separating filter according to claim 1, whereinsaid porous member does not adsorb platelets.
 3. Theleukocyte-separating filter according to claim 1, wherein at least oneof said three-dimensionally reticular, porous members is made of aplatelet-adsorbing material.